A number of non-coding RNAs have been discovered in the last few years, the best characterized of which are a family of 21-23 nucleotide RNAs referred to as microRNAs (miRNAs). Vertebrate genomes encode hundreds of miRNAs that regulate gene expression at the post-transcriptional level, primarily through repression of translation. Despite progress in elucidating the processing pathways and effector complexes that carry out miRNA function, precious little is known about the exact target mRNAs controlled by miRNAs. We have been using zebrafish as a model system to identify miRNA targets. Here, we propose to perform microarrays to identify miRNAs that are differentially expressed during zebrafish retinal regeneration and then functionally test the involvement of such miRNAs to identify key genes and regulatory cascades that control retinal regeneration. PUBLIC HEALTH RELEVANCE: For humans, increased life span will increase the numbers of patients suffering from one or more eye diseases. Currently, blindness or impaired vision affects over 3 million Americans but that number is expected to increase to over 5 million just by 2020 (Archives of Opthalmology, April, 2004) (Ferris III and Tielsch, 2004). Many diseases of the human eye involve loss, damage or degeneration of photoreceptor cells but in contrast to fish, regeneration is mostly absent. This proposal seeks to understand the mechanisms of retinal regeneration in the hopes that understanding the signals that allow such regeneration might identify therapeutic targets to restore or preserve photoreceptors.